Markers of Immune Activation and Inflammation in Individuals With Postacute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Abstract

Background: The biological processes associated with postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) are unknown.

Methods: We measured soluble markers of inflammation in a SARS-CoV-2 recovery cohort at early (<90 days) and late (>90 days) timepoints. We defined PASC as the presence of 1 or more coronavirus disease 2019 (COVID-19)-attributed symptoms beyond 90 days. We compared fold-changes in marker values between those with and without PASC using mixed-effects models with terms for PASC and early and late recovery time periods.

Results: During early recovery, those who went on to develop PASC generally had higher levels of cytokine biomarkers including tumor necrosis factor-α (1.14-fold higher mean ratio [95% confidence interval {CI}, 1.01-1.28]; P = .028) and interferon-γ-induced protein 10 (1.28-fold higher mean ratio [95% CI, 1.01-1.62]; P = .038). Among those with PASC, there was a trend toward higher interleukin 6 levels during early recovery (1.29-fold higher mean ratio [95% CI, .98-1.70]; P = .07), which became more pronounced in late recovery (1.44-fold higher mean ratio [95% CI, 1.11-1.86]; P < .001). These differences were more pronounced among those with a greater number of PASC symptoms.

Conclusions: Persistent immune activation may be associated with ongoing symptoms following COVID-19. Further characterization of these processes might identify therapeutic targets for those experiencing PASC.

Keywords: COVID-19; IL-6; PASC; SARS-CoV-2; TNF-α; biomarker; coronavirus; immune activation; inflammation; long COVID; postacute sequelae of SARS-CoV-2 infection.

Figure 1.

Cross-sectional levels of biomarkers among those with and without PASC during late recovery. Abbreviations: IFN-γ, interferon gamma; IgG, immunoglobulin G; IL-6, interleukin 6; IL-10, interleukin 10; IP-10, interferon-γ–induced protein 10; MCP-1, monocyte chemoattractant protein 1; PASC, postacute sequelae of severe acute respiratory syndrome coronavirus 2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-α, tumor necrosis factor alpha.

Figure 2.

Longitudinal changes in levels of biomarkers among individuals with and without PASC during late recovery. Abbreviations: IFN-γ, interferon gamma; IgG, immunoglobulin G; IL-6, interleukin 6; IL-10, interleukin 10; IP-10, interferon gamma–induced protein 10; MCP-1, monocyte chemoattractant protein 1; PASC, postacute sequelae of severe acute respiratory syndrome coronavirus 2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-α, tumor necrosis factor alpha.